Identification of non-amidine inhibitors of acid-sensing ion channel-3 (ASIC3)

Scott D Kuduk; Ronald K Chang; Christina N Di Marco; Robert M Dipardo; Sean P Cook; Matthew J Cato; Aneta Jovanovska; Mark O Urban; Michael Leitl; Robert H Spencer; Stefanie A Kane; George D Hartman; Mark T Bilodeau

doi:10.1016/j.bmcl.2011.05.064

Identification of non-amidine inhibitors of acid-sensing ion channel-3 (ASIC3)

Bioorg Med Chem Lett. 2011 Jul 15;21(14):4255-8. doi: 10.1016/j.bmcl.2011.05.064. Epub 2011 May 27.

Authors

Scott D Kuduk¹, Ronald K Chang, Christina N Di Marco, Robert M Dipardo, Sean P Cook, Matthew J Cato, Aneta Jovanovska, Mark O Urban, Michael Leitl, Robert H Spencer, Stefanie A Kane, George D Hartman, Mark T Bilodeau

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, Sumneytown Pike, PO Box 4, West Point, PA 19486, USA. [email protected]

PMID: 21669528
DOI: 10.1016/j.bmcl.2011.05.064

Abstract

A series of benzothiophene methyl amines were examined in an effort to identify non-amidine chemotypes with reduced polypharmacology from existing leads with the goal of finding potent ASIC3 channel blockers to advance the therapeutic evaluation of ASIC3 inhibition.

MeSH terms

Acid Sensing Ion Channels
Amidines / chemistry
Amiloride / chemistry
Animals
Nerve Tissue Proteins / antagonists & inhibitors*
Nerve Tissue Proteins / metabolism
Rats
Sodium Channel Blockers / chemistry*
Sodium Channel Blockers / pharmacology
Sodium Channels / metabolism
Structure-Activity Relationship

Substances

ASIC3 protein, rat
Acid Sensing Ion Channels
Amidines
Nerve Tissue Proteins
Sodium Channel Blockers
Sodium Channels
Amiloride